Our group has operated in five basic areas: bone marrow transplantation, hybrid tumor cells, murine tumor viruses, drug effects on macromolecules, DNA synthetic enzymes. There is evidence that AML may be a stem cell defect. Consequently, a program of early bone marrow transplantation has been undertaken. The characteristics of human GVH disease have been studied and an assay for the diagnosis of acute and chronic GVH disease has been developed using a microtiter fibroblast cytotoxicity assay. Cytotoxic drug effects are being compared in resting vs. growing 3T6 fibroblast cultures. The mechanism of action of methotrexate is being re-evaluated. Brain tumors may have altered metabolic pathways resulting in potential selective toxicity for some chemotherapeutic agents. The study of the mechanisms of leukemic transformation by murine oncogenic viruses has resulted in a direct transformation assay for hematopoietic cells. In addition, a human serum factor needed for the growth of non-transformed 3T3 cells has been isolated, characterized, and quantitated. Terminal dioxynucleotidyl transferase (TdT) is a distinct biochemical property of acute lymphoblastic leukemia. A fluorescent antibody assay has been developed. Normal thymus and normal bone marrows also contain TdT, but the enzyme has different chromatographic properties.